Mars Perihelion Cloud Trails as revealed by MARCI: Mesoscale Topographically Focussed Updrafts and Gravity Wave Forcing of High Altitude Clouds.

Daily, global wide angle imaging of Mars clouds in MARCI (MARs Color Imager, (Malin et al., 2008)) ultraviolet and visible bands reveals the spatial/seasonal distributions and physical characteristics of perihelion cloud trails (PCT); a class of high altitude (40-50 km), horizontally extended (200-1000 km, trending W to WSW) water ice clouds formed over specific southern low-to-mid latitude (5S-40S), mesoscale (~50 km) locations during the Mars perihelion, southern summer season. PCT were first reported in association with rim regions of Valles Marineris (Clancy et al., 2009). The current study employs MARCI 2007-2011 imaging to sample the broader distributions and properties of PCT; and indicates several distinct locations of peak occurrences, including SW Arsia Mons, elevated regions of Syria, Solis, and Thaumasia Planitia, along Valles Marineris margins, and the NE rim of Hellas Basin. PCT are present over Mars solar longitudes (L S ) of 210-310°, in late morning to mid afternoon hours (10am-3pm), and are among the brightest and most distinctive clouds exhibited during the perihelion portion of the Mars orbit. Their locations (i.e., eastern margin origins) correspond to strong local elevation gradients, and their timing to peak solar heating conditions (perihelion, subsolar latitudes and midday local times). They occur approximately on a daily basis among all locations identified (i.e., not daily at a single location). Based on cloud surface shadow analyses, PCT form at 40-50 km aeroid altitudes, where water vapor is generally at near-saturation conditions in this perihelion period (e.g. Millour et al., 2014). They exhibited notable absences during periods of planet encircling and regional dust storm activity in 2007 and 2009, respectively, presumably due to reduced water saturation conditions above 35-40 km altitudes associated with increased dust heating over the vertically extended atmosphere (e.g., Neary et al., 2019). PCT exhibit smaller particle sizes (R eff =0.2-0.5µm) than typically exhibited in the lower atmosphere, and incorporate significant fractions of available water vapor at these altitudes. PCT ice particles are inferred to form continuously (over ~4 hours) at their PCT eastern origins, associated with localized updrafts, and are entrained in upper level zonal/meridional winds (towards W or WSW with ~50 m/sec speeds at 40-50 km altitudes) to create long, linear cloud trails. PCT cloud formation is apparently forced in the lower atmosphere (≤10-15 km) by strong updrafts associated with distinctive topographic gradients, such as simulated in mesoscale studies (e.g., Tyler and Barnes, 2015) and indicated by the surface-specific PCT locations. These lower scale height updrafts are proposed to generate vertically propagating gravity waves (GW), leading to PCT formation above ~40 km altitudes where water vapor saturation conditions promote vigorous cloud ice formation. Recent mapping of GW amplitudes at ~25 km altitudes, from Mars Climate Sounder 15 µm radiance variations (Heavens et al., 2020), in fact demonstrates close correspondences to the detailed spatial distributions of observed PCT, relative to other potential factors such as surface albedo and surface elevation (or related boundary layer depths).

Atrial GIRK Channels Mediate the Effects of Vagus Nerve Stimulation on Heart Rate Dynamics and Arrhythmogenesis.

Diminished parasympathetic influence is central to the pathogenesis of cardiovascular diseases, including heart failure and hypertension. Stimulation of the vagus nerve has shown promise in treating cardiovascular disease, prompting renewed interest in understanding the signaling pathway(s) that mediate the vagal influence on cardiac physiology. Here, we evaluated the contribution of G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels to the effect of vagus nerve stimulation (VNS) on heart rate (HR), HR variability (HRV), and arrhythmogenesis in anesthetized mice. As parasympathetic fibers innervate both atria and ventricle, and GIRK channels contribute to the cholinergic impact on atrial and ventricular myocytes, we collected in vivo electrocardiogram recordings from mice lacking either atrial or ventricular GIRK channels, during VNS. VNS decreased HR and increased HRV in control mice, in a muscarinic receptor-dependent manner. This effect was preserved in mice lacking ventricular GIRK channels, but was nearly completely absent in mice lacking GIRK channels in the atria. In addition, atrial-specific ablation of GIRK channels conferred resistance to arrhythmic episodes induced by VNS. These data indicate that atrial GIRK channels are the primary mediators of the impact of VNS on HR, HRV, and arrhythmogenesis in the anesthetized mouse.

Stochastic vagus nerve stimulation affects acute heart rate dynamics in rats.

Vagus nerve stimulation (VNS) is an approved therapy for treatment of epilepsy and depression. While also shown to be promising in several preclinical and clinical studies to treat cardiovascular diseases, optimal therapeutic stimulation paradigms are still under investigation. Traditionally, parameters such as frequency, current, and duty cycle are used to adjust the efficacy of VNS therapy. This study explored the effect of novel stochastic VNS (S-VNS) on acute heart rate (HR) dynamics. The effect of S-VNS was evaluated in Sprague Dawley rats by comparing the acute HR and HR variability (HRV) responses to standard, periodic VNS (P-VNS) across different frequencies (FREQs, 10-30 Hz). Our results demonstrate that both S-VNS and P-VNS produced negative chronotropic effects in a FREQ-dependent manner with S-VNS inducing a significantly smaller drop in HR at 10 Hz and 20 Hz compared to P-VNS (p<0.05). S-VNS demonstrated a FREQ-dependent drop in the SD1/SD2 ratio, a measure of HRV, which was absent in P-VNS, suggesting that S-VNS may acutely modulate the nonlinear relationship between short- and long-term HRV. In conclusion, S-VNS is a novel stimulation procedure that may provide different physiological outcomes from standard P-VNS, as indicated by our analysis of HR dynamics. Our study provides a rationale for further detailed investigations into the therapeutic potential of S-VNS as a novel neuromodulation technique.

Real-Time Closed Loop Diastolic Interval Control Prevents Cardiac Alternans in Isolated Whole Rabbit Hearts.

Cardiac alternans, a beat-to-beat alternation in action potential duration (APD), can lead to fatal arrhythmias. During periodic pacing, changes in diastolic interval (DI) depend on subsequent changes in APD, thus enhancing cardiac instabilities through a 'feedback' mechanism. Recently, an anti-arrhythmic Constant DI pacing protocol was proposed and shown to be effective in suppressing alternans in 0D and 1D in silico studies. However, previous experimental validation of Constant DI pacing in the heart has been unsuccessful due to the spatio-temporal complexity of 2D cardiac tissue and the technical challenges in its real-time implementation. Here, we developed a novel closed loop system to detect T-waves from real-time ECG data, enabling successful implementation of Constant DI pacing protocol, and performed high-resolution optical mapping experiments on isolated whole rabbit hearts to validate its anti-arrhythmic effects. The results were compared with: (1) Periodic pacing (feedback inherent) and (2) pacing with heart rate variability (HRV) (feedback modulation) introduced by using either Gaussian or Physiological patterns. We observed that Constant DI pacing significantly suppressed alternans in the heart, while maintaining APD spatial dispersion and flattening the slope of the APD restitution curve, compared to traditional Periodic pacing. In addition, introduction of HRV in Periodic pacing failed to prevent cardiac alternans, and was arrhythmogenic.

Chronic cyclic vagus nerve stimulation has beneficial electrophysiological effects on healthy hearts in the absence of autonomic imbalance.

Cardiovascular disease degrades the regulatory function of the autonomic nervous system. Cyclic vagus nerve stimulation (VNS) is an already FDA-approved therapy for drug-resistant epilepsy and depression, and has been shown to normalize autonomic function and improve objective measures of heart function and subjective measures of heart failure symptoms. However, it remains unclear whether VNS may induce negative effects in patients with potentially healthy hearts where VNS can be used for epileptic patients. Hence, this study aims to investigate the effects of VNS on the hearts of healthy rats with normal autonomic balance. Sprague-Dawley rats were implanted with stimulators and randomized to either Sham or VNS groups. Rats in VNS group received 10 weeks of chronic intermittent VNS via stimulation of the right cervical vagus nerve. Echocardiography was performed at Baseline (prior to VNS), Week 2, and Week 9. After 10 weeks, high-resolution optical mapping was performed in ex vivo perfused hearts to evaluate the electrophysiological remodeling that occurs in the heart as a result of the VNS therapy. Chronic VNS modified the electrophysiological properties of healthy rat hearts by reducing the action potential duration at 50% (APD50) and 80% (APD80) repolarization. Chronic VNS also affected the restitution properties of the heart at the APD50 level and increased myocardial conduction velocity (CV). VNS did not induce any significant changes to ventricular ejection fraction (EF) and spatial dispersion of APD, thus indicating that VNS did not negatively affect cardiac function. VNS also reduced the susceptibility to ventricular arrhythmias (ventricular fibrillation [VF] and ventricular tachycardia [VT]) during ex vivo programmed electrical stimulation. In summary, chronic application of cyclic VNS induces changes to the electrophysiological properties of healthy rat hearts. The observed decrease in APD and increase in CV suggest that the beneficial effects of VNS do not require the presence of existing autonomic imbalance.

Pro-arrhythmic effect of heart rate variability during periodic pacing.

Clinically, healthy hearts have been associated with a high ventricular heart rate variability (HRV) while diseased hearts have been known to exhibit low ventricular HRV. Hence, low HRV is suggested to be a marker of cardiac ventricular arrhythmias. Over the past few years, there has been considerable amount of interest in incorporating HRV in pacing to emulate healthy heart conditions and re-stabilize the electrical activity in diseased hearts. Recently, we used single cell numerical simulations to demonstrate that HRV incorporated into periodic pacing promotes alternans formation and thus, can be pro-arrhythmic. Here, we performed high-resolution optical mapping experiments on Langendorff perfused, healthy whole mice hearts to validate our numerical findings. Our results indeed demonstrate that HRV promoted the onset of cardiac alternans, which is believed to be a precursor of fatal cardiac rhythms. Hence, our present study suggests that incorporating HRV into periodic pacing while addressing several clinical needs may not be safe. There is a pressing need to better understand paced cardiac dynamics and develop anti-arrhythmic pacing techniques that would prevent cardiac arrhythmias.

Intermittent electrical stimulation of the right cervical vagus nerve in salt-sensitive hypertensive rats: effects on blood pressure, arrhythmias, and ventricular electrophysiology.

Hypertension (HTN) is the single greatest risk factor for potentially fatal cardiovascular diseases. One cause of HTN is inappropriately increased sympathetic nervous system activity, suggesting that restoring the autonomic nervous balance may be an effective means of HTN treatment. Here, we studied the potential of vagus nerve stimulation (VNS) to treat chronic HTN and cardiac arrhythmias through stimulation of the right cervical vagus nerve in hypertensive rats. Dahl salt-sensitive rats (n = 12) were given a high salt diet to induce HTN. After 6 weeks, rats were randomized into two groups: HTN-Sham and HTN-VNS, in which VNS was provided to HTN-VNS group for 4 weeks. In vivo blood pressure and electrocardiogram activities were monitored continuously by an implantable telemetry system. After 10 weeks, rats were euthanized and their hearts were extracted for ex vivo electrophysiological studies using high-resolution optical mapping. Six weeks of high salt diet significantly increased both mean arterial pressure (MAP) and pulse pressure, demonstrating successful induction of HTN in all rats. After 4 weeks of VNS treatment, the increase in MAP and the number of arrhythmia episodes in HTN-VNS rats was significantly attenuated when compared to those observed in HTN-Sham rats. VNS treatment also induced changes in electrophysiological properties of the heart, such as reduction in action potential duration (APD) during rapid drive pacing, slope of APD restitution, spatial dispersion of APD, and increase in conduction velocity of impulse propagation. Overall, these results provide further evidence for the therapeutic efficacy of VNS in HTN and HTN-related heart diseases.

Intermittent vagal nerve stimulation alters the electrophysiological properties of atrium in the myocardial infarction rat model.

Intermittent vagal nerve stimulation (VNS) has emerged as a potential therapy to treat cardiovascular diseases by delivering electrical stimulation to the vagus nerves. The purpose of this study was to investigate the electrophysiological changes in the atrium resulting from long-term intermittent VNS therapy in the chronic myocardial infarction (MI) rat model. MI was induced via left anterior descending coronary artery (LAD) ligation in male Sprague-Dawley rats, randomized into two groups: MI (implanted with nonfunctional VNS stimulators) and MI-VNS (implanted with functional VNS stimulators and received chronic intermittent VNS treatment) groups. Further, a sham group was used as control in which MI was not performed and received nonfunctional VNS stimulators. At 12 weeks, optical mapping of right atrium (RA) of sinus rhythm was performed. Our results demonstrated that chronic MI changed the electrical properties of the atrium action potentials and resulted in reduced action potential duration at 50% (APD50) and 80% (APD80) repolarization. Chronic right cervical VNS restored the APD back to healthy heart APD values. Additionally, APD heterogeneity index increased as a result of the chronic MI. Chronic VNS was not found to alter this increase. By calculating PR intervals from weekly ECG recordings of anaesthetized rats, we demonstrated that chronic MI and intermittent VNS did not affect the AV conduction time from the atria to the ventricles. From our study, we conclude the MI decreased the APD and increased APD spatial dispersion. VNS increased the APD back to healthy normal values but did change the APD spatial dispersion and the electrical conduction in the RA.

Significant predictors of test anxiety among students with and without learning disabilities.

In the present study, the relationship between students with and without learning disabilities (LD) and different aspects of test anxiety was examined on a new multidimensional measure of test anxiety. A sample of 774 elementary and secondary school students--195 students with LD and 579 students not identified with LD--completed the Test Anxiety Inventory for Children and Adolescents (TAICA), a new multidimensional measure of test anxiety for elementary and secondary school students in Grades 4 through 12. Examination of the factor structure of the TAICA scores across LD status to determine whether accurate test score interpretation was possible revealed that the majority of the coefficient of congruence values between each pair of six corresponding factors of the TAICA (Cognitive Obstruction/ Inattention, Performance Enhancement/Facilitation Anxiety, Physiological Hyperarousal, Social Humiliation, Worry, and Lie) and the Total Test Anxiety factor were above .90, and the salient variable similarity index values were statistically significant, suggesting that the factor structure of the TAICA was similar across groups. The results of seven multiple regression analyses revealed that LD predicted higher Cognitive Obstruction/Inattention and Worry scores and lower Performance Enhancement/Facilitation Anxiety and Lie scores. Implications of the findings for school personnel who work with students with LD are discussed.